PT  - JOURNAL ARTICLE
AU  - Robert J. Ertel
AU  - Franz Halberg
AU  - Frank Ungar
TI  - CIRCADIAN SYSTEM PHASE-DEPENDENT TOXICITY AND OTHER EFFECTS OF METHOPYRAPONE (SU-4885) IN THE MOUSE
DP  - 1964 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 395--399
VI  - 146
IP  - 3
4099  - http://jpet.aspetjournals.org/content/146/3/395.short
4100  - http://jpet.aspetjournals.org/content/146/3/395.full
SO  - J Pharmacol Exp Ther1964 Dec 01; 146
AB  - Blood corticosterone levels in Bagg albino and certain hybrid mice are greatly depressed by 20 mg/kg of methopyrapone (SU-4885) at 20 minutes postinjection. Doses higher than 200 mg/kg produced a general anesthesia and doses from 300 to 400 mg/kg of SU-4885 were lethal in several strains of mice. Moreover, three toxicity experiments, carried out by indirect periodicity analysis, revealed a statistically significant circadian rhythm in the susceptibility of the male C or CD2D2 mouse to the early lethal effects of SU-4885. Under appropriately standardized conditions the number of deaths occurring within 6 hours after the injection of SU-4885 (into separate groups of comparable mice injected at 4-hour intervals during 24-hour periods) depended upon the circadian system phase at the time of drug administration. The amplitude of this circadian susceptibility-resistance cycle to SU-4885 was large, involving under certain conditions, changes of over 50% around the mean. As to its external timing, the circadian rhythmic increase in susceptibility to methopyrapone occurred prior to the beginning of the daily dark period in mice kept on a regimen of 12 hours of light alternating with 12 hours of darkness. The findings extend the scope of circadian system analysis in the study of respouses to drugs. The Williams & Wilkins Comapny